The long-term objective of the proposed research is to clarify the importance of one supposed factor in atherogenesis, hypoxia, and suggest possible measures to improve vascular oxygenation and thereby reduce atherogenesis. The arterial wall with its luminal side apparently completely avascular has a particularly precarious oxygen supply system. It has long been supposed that the hypoxia associated with failure of this system is somehow implicated as one factor in the etiology of arterial wall disease. Arterial wall hyperoxia is believed to be beneficial in both protecting against, and even reversing, atherosclerosis. We propose to analyze the mural oxygen supply system by using ultramicro oxygen electrodes to measure steady oxygen profiles across the wall, and oxygen transients at points within wall, under various physiological and pathological conditions. Oxygen microelectrodes will be passed slowly through the arterial wall and the resulting oxygen tension profiles related to the important structures of the wall using histological sections along the needle track. Tissue oxygen transients, measured at known depths, will allow us to compare the oxygen permeabilities of the various mural structures of healthy and diseased walls. Oxygen profiles will be measured with luminal fluids of various oxygen tensions to determine the critical hypoxic limits both with and without perfusion of the vasa vasorum. Also, the luminal flow conditions will be varied to determine their effecs on oxygen transport to the wall, in particular whether or not pulsatile flow enhances transport. This study will provide important data needed for the mathematical modelling of this physiological mass transport system. An important phase in this research program will be a computer simulation of the arterial wall oxygen transport system in both health and disease.